Site and mechanism of growth inhibition by prostaglandins. IV. Effect of cyclopentenone prostaglandins on cell cycle progression of G1-enriched HeLa S3 cells.

HeLa S3 cells were enriched in the G1 phase of cell cycle by serum starvation and used for analysis of prostaglandin (PG) effect on cell cycle progression. Cell cycle progression was initiated by incubating the G1-enriched cells with fresh medium containing 10% fetal calf serum and analyzed in the presence of 40 nM colcemid to block renewal of the cycle. When progression of control cells was analyzed under these conditions, time-dependent decrease in the number of G1 phase cells and increase in that of G2/M phase cells were observed during the 24-hr incubation. Cells in S phase increased transiently during this period. Proportions of cells in G1 and G2/M phases were 65 and 15% of the total cells at 0 hr and 10 and 80% at 24 hr, respectively. When the cells were treated with either PGA2 or 9-deoxy-delta 9,12-13,14-dihydroprostaglandin D2 (delta 12-PGJ2) for more than 3 hr, inhibition of G1 phase progression became evident 3 to 6 hr after the PG addition. Progression through S phase was slowed but not arrested with the PG treatment. When cells treated with PGA2 were washed and transferred to fresh medium, G1 phase progression was resumed and transition to S phase was observed about 6 hr after the wash. However, the arrest by delta 12-PGJ2 was irreversible and no recovery was observed with washing of the cells treated with this PG. The sensitivities of cells to PG in different phases of cell cycle were compared by treating G2/M phase cells with delta 12-PGJ2.(ABSTRACT TRUNCATED AT 250 WORDS)